scholarly journals Synaptic mitochondria regulate hair-cell synapse size and function

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hiu-tung C Wong ◽  
Qiuxiang Zhang ◽  
Alisha J Beirl ◽  
Ronald S Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Direct Application ◽  
Structural Protein ◽  
Ribbon Synapses ◽  
Presynaptic Function ◽  
Sensory Hair Cells ◽  
Synaptic Mitochondria ◽  
And Function ◽  
Cell Synapse

Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through CaV1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic-Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic-Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD+/NADH redox and downregulates ribbon size. Direct application of NAD+ or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.

scholarly journals Synaptic mitochondria are critical for hair-cell synapse formation and function

2019 ◽  
Author(s):  
Hiu-tung C. Wong ◽  
Qiuxiang Zhang ◽  
Alisha J. Beirl ◽  
Ronald S. Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Synapse Formation ◽  
Direct Application ◽  
Structural Protein ◽  
Ribbon Synapses ◽  
Presynaptic Function ◽  
Sensory Hair Cells ◽  
And Function ◽  
Cell Synapse

SummarySensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+through CaV1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+influx through CaV1.3 channels initiates mitochondrial-Ca2+(mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+uptake in mature cells depresses presynaptic Ca2+influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+uptake coincides with spontaneous rises in presynaptic Ca2+influx. Spontaneous mito-Ca2+loading lowers cellular NAD+/NADH redox and downregulates ribbon formation. Direct application of NAD+or NADH increases or decreases ribbon formation respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+couple to confer proper presynaptic function and formation.

scholarly journals The quantal component of synaptic transmission from sensory hair cells to the vestibular calyx

2015 ◽  
Vol 113 (10) ◽  
pp. 3827-3835 ◽  
Author(s):  
Stephen M. Highstein ◽  
Mary Anne Mann ◽  
Gay R. Holstein ◽  
Richard D. Rabbitt
Keyword(s):  
Hair Cell ◽  
Time Constant ◽  
Hair Cells ◽  
Decay Time ◽  
Event Rate ◽  
Decay Time Constant ◽  
Ribbon Synapses ◽  
Diverse Species ◽  
Sensory Hair Cells ◽  
Cell Depolarization

Spontaneous and stimulus-evoked excitatory postsynaptic currents (EPSCs) were recorded in calyx nerve terminals from the turtle vestibular lagena to quantify key attributes of quantal transmission at this synapse. On average, EPSC events had a magnitude of ∼42 pA, a rise time constant of τ0 ∼229 μs, decayed to baseline with a time constant of τR ∼690 μs, and carried ∼46 fC of charge. Individual EPSCs varied in magnitude and decay time constant. Variability in the EPSC decay time constant was hair cell dependent and due in part to a slow protraction of the EPSC in some cases. Variability in EPSC size was well described by an integer summation of unitary quanta, with each quanta of glutamate gating a unitary postsynaptic current of ∼23 pA. The unitary charge was ∼26 fC for EPSCs with a simple exponential decay and increased to ∼48 fC for EPSCs exhibiting a slow protraction. The EPSC magnitude and the number of simultaneous unitary quanta within each event increased with presynaptic stimulus intensity. During tonic hair cell depolarization, both the EPSC magnitude and event rate exhibited adaptive run down over time. Present data from a reptilian calyx are remarkably similar to noncalyceal vestibular synaptic terminals in diverse species, indicating that the skewed EPSC size distribution and multiquantal release might be an ancestral property of inner ear ribbon synapses.

scholarly journals Author response: Synaptic mitochondria regulate hair-cell synapse size and function

2019 ◽  
Author(s):  
Hiu-tung C Wong ◽  
Qiuxiang Zhang ◽  
Alisha J Beirl ◽  
Ronald S Petralia ◽  
Ya-Xian Wang ◽  
...  
Keyword(s):  
Hair Cell ◽  
Author Response ◽  
Synaptic Mitochondria ◽  
And Function ◽  
Cell Synapse

scholarly journals The microRNA-183/96/182 Cluster is Essential for Stereociliary Bundle Formation and Function of Cochlear Sensory Hair Cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ruishuang Geng ◽  
David N Furness ◽  
Chithra K Muraleedharan ◽  
Jinsheng Zhang ◽  
Alain Dabdoub ◽  
...  
Keyword(s):  
Hair Cells ◽  
Sensory Hair ◽  
Sensory Hair Cells ◽  
And Function

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 557-566 ◽  
Author(s):  
T. Self ◽  
M. Mahony ◽  
J. Fleming ◽  
J. Walsh ◽  
S.D. Brown ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Usher Syndrome ◽  
Orthologous Gene ◽  
Cell Development ◽  
Cochlear Hair Cells ◽  
Cochlear Hair Cell ◽  
Show Evidence ◽  
Myosin Viia ◽  
And Function

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

scholarly journals Structure and function of the Nautilus statocyst

1997 ◽  
Vol 352 (1361) ◽  
pp. 1565-1588 ◽  
Author(s):  
H. Neumeister ◽  
B. U. Budelmann
Keyword(s):  
Hair Cells ◽  
Stripe Pattern ◽  
White Stripe ◽  
Black And White ◽  
Visual Inputs ◽  
Sensory Hair Cells ◽  
Sinusoidal Oscillations ◽  
Gravity Receptor ◽  
Behavioural Experiments ◽  
And Function

The two equilibrium receptor organs (statocysts) of Nautilus are ovoid sacks, half-filled with numerous small, free-moving statoconia and half with endolymph. The inner surface of each statocyst is lined with 130 000 to 150 000 primary sensory hair cells. The hair cells are of two morphological types. Type A hair cells carry 10 to 15 kinocilia arranged in a single ciliary row; they are present in the ventral half of the statocyst. Type B hair cells carry 8 to 10 irregularly arranged kinocilia; they are present in the dorsal half of the statocyst. Both type of hair cells are morphologically polarized. To test whether these features allow the Nautilus statocyst to sense angular accelerations, behavioural experiments were performed to measure statocyst-dependent funnel movements during sinusoidal oscillations of restrained Nautilus around a vertical body axis. Such dynamic rotatory stimulation caused horizontal phase-locked movements of the funnel. The funnel movements were either in the same direction (compensatory funnel response), or in the opposite direction (funnel follow response) to that of the applied rotation. Compensatory funnel movements were also seen during optokinetic stimulation (with a black and white stripe pattern) and during stimulations in which optokinetic and statocyst stimulations were combined. These morphological and behavioural findings show that the statocysts of Nautilus , in addition to their function as gravity receptor organs, are able to detect rotatory movements (angular accelerations) without the specialized receptor systems (crista/cupula systems) that are found in the statocysts of coleoid cephalopods. The findings further indicate that both statocyst and visual inputs control compensatory funnel movements.

scholarly journals The challenge of hair cell regeneration

2010 ◽  
Vol 235 (4) ◽  
pp. 434-446 ◽  
Author(s):  
Andrew K Groves
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Electrical Energy ◽  
Cell Regeneration ◽  
Hair Cell Regeneration ◽  
Therapeutic Approaches ◽  
Auditory Hair Cells ◽  
Sensory Hair Cells ◽  
Ototoxic Drugs ◽  
Effects Of Aging

Sensory hair cells of the inner ear are responsible for translating auditory or vestibular stimuli into electrical energy that can be perceived by the nervous system. Although hair cells are exquisitely mechanically sensitive, they can be easily damaged by excessive stimulation by ototoxic drugs and by the effects of aging. In mammals, auditory hair cells are never replaced, such that cumulative damage to the ear causes progressive and permanent deafness. In contrast, non-mammalian vertebrates are capable of replacing lost hair cells, which has led to efforts to understand the molecular and cellular basis of regenerative responses in different vertebrate species. In this review, we describe recent progress in understanding the limits to hair cell regeneration in mammals and discuss the obstacles that currently exist for therapeutic approaches to hair cell replacement.

scholarly journals Cnr2 Is Important for Ribbon Synapse Maturation and Function in Hair Cells and Photoreceptors

2021 ◽  
Vol 14 ◽  
Author(s):  
Luis Colón-Cruz ◽  
Roberto Rodriguez-Morales ◽  
Alexis Santana-Cruz ◽  
Juan Cantres-Velez ◽  
Aranza Torrado-Tapias ◽  
...  
Keyword(s):  
Hair Cells ◽  
Cannabinoid Receptor ◽  
Sensory Information ◽  
Endocannabinoid System ◽  
Cannabinoid Receptor 2 ◽  
Ribbon Synapses ◽  
Sensory Epithelia ◽  
Synapse Maturation ◽  
And Function

The role of the cannabinoid receptor 2 (CNR2) is still poorly described in sensory epithelia. We found strong cnr2 expression in hair cells (HCs) of the inner ear and the lateral line (LL), a superficial sensory structure in fish. Next, we demonstrated that sensory synapses in HCs were severely perturbed in larvae lacking cnr2. Appearance and distribution of presynaptic ribbons and calcium channels (Cav1.3) were profoundly altered in mutant animals. Clustering of membrane-associated guanylate kinase (MAGUK) in post-synaptic densities (PSDs) was also heavily affected, suggesting a role for cnr2 for maintaining the sensory synapse. Furthermore, vesicular trafficking in HCs was strongly perturbed suggesting a retrograde action of the endocannabinoid system (ECs) via cnr2 that was modulating HC mechanotransduction. We found similar perturbations in retinal ribbon synapses. Finally, we showed that larval swimming behaviors after sound and light stimulations were significantly different in mutant animals. Thus, we propose that cnr2 is critical for the processing of sensory information in the developing larva.

scholarly journals Multiple PDZ domain protein maintains patterning of the apical cytoskeleton in sensory hair cells

Development ◽  
2021 ◽  
Author(s):  
Amandine Jarysta ◽  
Basile Tarchini
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Critical Role ◽  
Pdz Domain ◽  
Hair Bundle ◽  
Structural Defects ◽  
Sensory Hair ◽  
High Frequencies ◽  
Sensory Hair Cells ◽  
Sound Transduction

Sound transduction occurs in the hair bundle, the apical compartment of sensory hair cells in the inner ear. The hair bundle is formed of actin-based stereocilia aligned in rows of graded heights. It was previously shown that the GNAI-GPSM2 complex is part of a developmental blueprint that defines the polarized organization of the apical cytoskeleton in hair cells, including stereocilia distribution and elongation. Here we report a novel and critical role for Multiple PDZ domain (MPDZ) protein during apical hair cell morphogenesis. We show that MPDZ is enriched at the hair cell apical membrane along with MAGUK p55 subfamily member 5 (MPP5/PALS1) and the Crumbs protein CRB3. MPDZ is required there to maintain the proper segregation of apical blueprints proteins, including GNAI-GPSM2. Loss of the blueprint coincides with misaligned stereocilia placement in Mpdz mutant hair cells, and results in permanently misshapen hair bundles. Graded molecular and structural defects along the cochlea can explain the profile of hearing loss in Mpdz mutants, where deficits are most severe at high frequencies.

Sign in / Sign up

Export Citation Format

Share Document